Complications of fast neutron therapy

The purpose of the study was to identify the tissues and organs at risk following high-energy neutron-beam therapy for selected radioresistant tumors, estimating the separate probabilities of both normal tissue injury and of tumor recurrence, each in relation to the absorbed dose. Published statistical and anecdotal reports on the incidence of serious complications observed following fast neutron treatment directed to the cranium, head and neck, chest, upper abdomen, pelvis, and extremities are reviewed and dose-response parameters derived using bivariate probit or logistic analyses. We then calculate the conditional probability of uncomplicated control (PUC) at various doses, assuming that tumor cure and late injury are stochastically independent events. The median effective doses and coefficients of variation, derived for neutron irradiation of human brain and spinal cord, oropharynx, lung, stomach and bowel, rectum and bladder, and extremities, are tabulated and tentative "tolerance limits" estimated. Tolerance doses are shown to depend on several factors including beam quality, chemical composition, cell cycling rate, fraction-size, and follow-up time. In patients followed over 5 years, safe tolerance doses appear to range from < 14 GY for the central nervous system up to 22 GY in the oropharynx and mandible. Given well-determined dose-response data for specific normal tissues and the associated tumors, the separate probabilities of tumor control and of normal tissue injury at a given dose can be estimated. The particular treatment scheme yielding the highest PUC can usually be identified. The maximum PUC for neutron therapy, compared with other modalities, is a measure of both efficacy and safety for the procedure under study and thus provides a useful guide for comparing various modalities and treatment plans and for designing more effective treatment strategies.